Fungicidal compositions



United States Patent 3,250,677 FUNGICIDAL COMPOSITIONS William E. Burt, Baton Rouge, La., assignor to Ethyl Corporation, New York, N.Y., a corporation of Virginia No Drawing. Filed Feb. 28, 1964, Ser. No. 348,258 19 Claims. (Cl. 16758) This invention relates to novel fungicidal compositions and their use in the treatment of fungal infections.

In my copending application Serial No. 161,367, filed December 22, 1961, now US. 3,123,523, of which this application is a continuation-in-part, I described the use of arene Group VIB metal tricarbonyls in the treatment of fungi which are pathogenic to animals, vegetables, and man. A preferred embodiment of the invention described in said earlier application comprises the treatment of fungi with a compound having the formula:

wherein M is a metal of Group VIB of the Periodic Table, X is a halogen; a is an integer having the value 0 to 1; Y is selected from the class comprising wherein R and R are alike or different and selected from the class consisting of hydrogen and alkyl groups having one to about 4 carbon atoms; b is an integer having the value 0 to 1; R is selected from the class consisting of hydrogen and alkyl groups having one to about 4 carbon atoms; and c is an integer having the value 0 to 3, such that when c=3, a=0 and b=0. Compounds of this type can be prepared by the general method of Nicholls et al., Proc. Chem. Soc. (1958), page 152.

When the subscripts a, b, and c, in the above formula are equal to zero, the compound is benzene chromium tricarbonyl. When the subscript a is equal to one, and b and c are both equal to zero, the compounds are the halobenzene tricarbonyls of the metals of Group VIB. Benzene chromium tricarbonyl and chlorobenzene chromium tricarbonyl are highly preferred compounds since the aromatic portion of the molecule is available at low cost.

When a and b are equal to zero and c has a value from one to three, the compounds are hydrocarbon substituted benzene metal tricarbonyls. This class of com-pounds is represented by the chromium tricarbonyls of toluene, o-diethylbenzene, o, m, p-xylenes, p-isobutyltoluene, mesitylene, and the like. The preferred compounds of this class are the compounds having methyl substituents on the benzene ring. The most preferred compounds are toluene chromium tricarbonyl, the xylene chromium tricarbonyls, and mesitylene chromium tricarbonyl.

When a and c are equal to zero and b is equal to one, the compounds are the chromium tricarbonyls of aniline, N,N-dimethylaniline, acetanilide, acetophenone, benzyl alcohol, methylbenzoate, and the like. The preferred compounds of this class are acetophenone chromium tricarbonyl, methylbenzoate chromium tricarbonyl, aniline chromium tricarbonyl, and N,N-dirnethylaniline chromium tricarbonyl.

When more than one of the subscripts in the above formula is equal to one, compounds such as the chromium tricarbonyls of o-toluidine, p-methylanisole, m-chloroaniline, and the like are described. The o-toluidine and p-methylanisole compounds are preferred because of their commercial availability.

This invention is directed to the provision of novel fungicidal compositions (which contain, as a principal active ingredient, a fungitoxic amount of one or more of the arene Group VIB metal tricarbonyls, described and formulated above) that are especially eflicacious in the treatment of external fungal infection of human beings. The provision of compositions of this type is a primary object of this invention. Another object is to provide solid, semi-solid, or liquid preparations (containing fungitoxic amounts of one or more arene Group VIB metal tricarbonyls) which can be applied to human epidermis.

The objects of this invention are satisfied by providing solid, semi-solid, or liquid preparations containing a fungitoxic amount of one or more arene Group VIB metal tricarbonyls in a lotion, ointment, salve, or cream base.

The fungicidal compositions of this invention have many inherent advantages. For example, not only do they contain a highly potent arene metal carbonyl, but they are readily prepared by methods well known to those skilled in the art of the preparation of lotions, ointments, salves, or creams. Furthermore, they are readily dispensed and applied to the locus of the fungi. Still another advantage of the compositions of this invention is that they provide a protective area over the infected part when applied to the locus of the fungi. Many of the preparations of this invention contain a high concentration of an insoluble oleaginous substance. Formulations of this type are not readily removed from the infected area by the rubbing of clothing or exposure to water. Hence, they provide a more permanent application than preparations such as dusts and solutions. Another advantage of the compositions of this invention is that the oleaginous substances, alcohols, and esters employed in their preparation have emollient properties which improve the texture of epidermis when applied thereto. Many of the compositions of this invention, especially those which contain an emulsion-type base, are not very visible when applied to an exposed area of the skin. Hence, they are highly acceptable from a cosmetic viewpoint. Furthermore, the formulations of this invention are more stable than many other fungicidal compositions containing arene Group VIB metal tricarbonyls. Thus, they have a longer shelf life and, therefore, are commercially attractive.

As stated above, many of the compositions of this invention contain a base comprising an oleaginous substance. The exact nature of'the oleaginous substance is not critical, provided that the substance is non-toxic and non-drying. By non-drying, I mean those oleaginous substances which tend to become more solid upon exposure to air. Hence, I preferably exclude high quantities of drying oils such as linseed oil and the like from my preparations. However, minor amounts of these drying oils, say up to about 3%, can be employed if desired.

In general, the oleaginous substance may be any nontoxic, non-drying, inert water-insoluble material such as the natural or synthetic oils, fat, and waxes. As appreciated in the art, waxes commonly are esters of long-chain fatty acids with long-chain fatty alcohols. Usually the alcohols are monohydric; that is, they contain only one hydroxy function per molecule. In general, the oils and fats are esters of long-chain fatty acids with glycerol. The oils are liquids at room temperature while the fats are not. Other substances which can be employed include higher paraffinic substances. Usually mixtures of these, such as mineral oil, paraflin wax, or petrolatum are employed. Polymers of alcohols such as polyethyleneglycols having a molecular weight within the range of 0.5% water.

about 1500 to about 4000 (Carbowaxes), and similar substances can also be employed if desired.

Common waxes which can be employed are beeswax or purified beeswax. Cetyl palmitate and spermaceti can also be employed. Fats and oils which may be employed include cocoa butter, peanut oil, rapeseed oil, coconut oil, olive oil, cod liver oil, whale oil, fish oil, and the like.

One preferred embodiment of this invention is a composition which contains a fungitoxic amount of an arene Group VIB metal tricarbonyl in a substantially nonaqueous lotion, salve, cream, or ointment base. These preparations comprise from about 30 parts per million to about 30% by weight of at least one arene Group VIB metal tricarbonyl in an oleaginous base which does not contain more than about 1% by weight of water. Preferred formulations of this type contain less than about Hence, this embodiment of this invention comprises:

(1) As a principal active ingredient, a fungitoxic amount of a compound havingFormula I, and

(2) As a carrier therefor, a substantially anhydrous, non-toxic, non-drying, inert oleaginous substance.

A preferred type of this class of compositions also contains, per each 100 parts by weight of oleaginous substance, from about 5 to about 70 parts of a compatible higheralcohol having from about 13 to about 30 carbon atoms. Alcohols of this type are illustrated by cetyl alcohol, ste-aryl alcohol, octadecyl alcohol, cholesterol, a mixture of the alcohols derived from lanolin by hydrolysis (lanolin alcohols), and the like. The alcohols in crease the emollient qualities of the formulations.

Another preferred type of fungicidal composition contains, per each 100 parts of oleaginous substance, from about 10 to about 50 parts of an insoluble, inert opaque solid. Solids used in this embodiment may be organic in nature such as stearic acid, starch, and the like, or inorganic, such as gypsum, mica, talc, apatite, bentonite, and the like. These substances thicken the preparation.

A highly preferred non-aqueous fungicidal composition of this invention comprises a fungitoxic amount of at least one arene Group VIB metal tricarbonyl and, as a carrier therefor, an oleaginous substance of the type groups containing from 3 to 8 carbon atoms and are further characterized by being branched on their alpha carbon atoms; such that the concentration of the arene Group VIB metal tricarbonyl is from about 30 parts per million to about 30% by weight, and the concentration of said hindered phenol is from about 0.001 to about 5%, and preferably from about 0.25 to about 3 percent, by weight. The hindered phenols stabilize the preparations from oxidative deterioration.

Typical phenols of Formula II include 4,4'-methylenebis(2,6-diisopropylphenol); 4,4'-methylenebis(2,6-di-secbutylphenol); 4,4-methylenebis(2-isopropyl-6-tert-butylphenol); 4,4methylenebis[2,6-di-(2-octyl)-phenol]; 4,4- methylenebis [2-sec-butyl-6-(2-hexyl) phenol} 4,4'-methylene bis [2-isopropyl-6-( 1,1,3 ,3-tetramethylbutyl phenol] and the like. I

The preferred class of compounds of this type includes 4,4 methylenebis(Z-tert-butyl-6-tert-amylphenol); 4,4- rnethylenebis(2,6-di-tert-amylphenol); 4,4'-methylenebis- [2,6-di-( l 1 ,3,3-tetramethylbutyl) phenol]; 4,4-methylenebis [2-tert-butyl-6-(l, 1,2,2-tetramethylpropyl)-phenol] and the like.

Formulations of the type described above are prepared by incorporating the desired amount of arene Group VIB metal tn'carbonyl in the quantity desired in the desired base. Typical bases of this type are described below.

BASE 1 A mixture having the following ingredients is prepared. All parts are by weight.

Parts Cholesterol l0 Stearyl alcohol 30 White wax 80 Wool fat (anhydrous) 150 White petrolatum 730 The ingredients are melted together on a water bath and mixed thoroughly. Thereafter, the mixture is removed from the bath and stirred until it congeals. Table I below further illustrates bases of this type. The numbers in the columns are parts by Weight.

TABLE 1 Bases Ingredient Lanolin (anhydrous) 5 5 15.6

Mineral Oil U.S.P White beeswax.

Carbowax 400 Hydrogenated cottonseed oil Cetyl alcohol.

Stearyl aloohoL Cholesterol.

Lanolin alcohols Glycerylmonostearatestearic a m'd Magnesium oleate.

1,2,6-hexanetrioL l H t wherein the groups designated'by R and R are alkyl BASE 13 This base is prepared by thoroughly blending 10 parts of starch U.S.P to the ingredients of Base 3 in Table l.

BASE 14 This base is prepared by adding and thoroughly mixing 50 parts of starch to the ingredients of Base 3.

BASE 15 This base is prepared by adding 50 parts of bentonite to the ingredients of Base 7 and thoroughly mixing the resultant mixture.

BASE 16 4,4-methylenebis(2,6-di-tert-butylphenol), 0.25 part, is thoroughly mixed with 100 parts of Base 7. A similar base is prepared by adding 2.0 parts of the phenol to 100 parts of Base 10.

The following example illustrates the substantially anhydrous oleaginous compositions of this invention. All parts are by weight unless otherwise noted.

Example I Methylbenzoate chromium tricarbonyl, 30 parts, is thoroughly mixed with 999,970 parts of Base 1. The resultant fungicidal composition has a concentration of arene chromium tricarbonyl equal to 30 parts per million.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500, and 700 parts per million of methylbenzoate chromium tricarbonyl are prepared.

More concentrated foams containing 0.1, 0.5, l, 3, 5, 7, 10, 15, 20, and 30 percent of arene chromium tricarbonyl are prepared by adding the requisite quantity'of methylbenzoate chromium tricarbonyl to Base 1.

Example II o-Xylene chromium tricarbonyl, 30 parts, is added to 999,970 parts of Base 5 to yield a fungicidal composition having 30 parts per million of arene chromium tricarbonyl.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500 and 700 parts per million of -o-xylene chromium tricarbonyl are prepared. More concentrated foams containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20, and 30 percent of arene chromium tricarbonyl are prepared by adding the requisite quantity of o-xylene chromium tricarbonyl to Base 5.

Example III p-Xylene chromium tricarbonyl, 30 parts, is added to 999,970 parts of Base 3 to yield a fungicidal composition having 30 parts per million of arene chromium tricarbonyl.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500 and 700 parts per million of p-xylene chromium tricarbonyl are prepared. More concentrated foams containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20, and 30 percent of arene chromium tricarbonyl are prepared by adding the requisite quantity of p-xylene chromium tricarbonyl to Base 3.

Example IV o-Toluidine chromium tricarbonyl, 30 parts, is added to 999,970 parts of Base 6 to yield a fungicidal composition having 30 parts per million of arene chromium tricarbonyl.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500 and 700 parts per million of o-toluidine chromium tricarbonyl are prepared. More concentrated foams containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20 and 30 percent of arene chromium tricarbonyl are prepared by adding the requisite quantity of o-toluidine chromium tricarbonyl to Base 6.

Example V Fungicidal compositions containing 0.1% of arene chromium tricarbonyl are prepared by adding one-partportions of toluene chromium tricarbonyl to 999-part portions of Bases 2, 4, 7, 8, 9, 10, 11 and 12. Similar preparations are prepared 'by adding similar quantities of anisole chromium tricarbonyl and acetophenone chromium tricarbonyl to similar quantities of the same bases. Similar formulations containing benzene chromium tricarbonyl, aniline chromium tricarbonyl, toluene chromium tricarbonyl, and aniline chromium tricarbonyl are also prepared.

Example VI Fungicidal compositions containing 0.5% of chlorobenzene chromium tricarbonyl are prepared by adding five-part-portions of chlorobenzene chromium tricarbonyl to 99S-part-portions of Bases 13, 14, 15 and 16.

Similarly, one-part-portions of benzene chromium tricarbonyl are added to 99-part-portions of Bases 13, 14, 15 and 16 to yield fungicidal compositions which contain 1% of benzene chromium tricarbonyl.

Five hundred-part-portions of o-toluidine chromium tricarbonyl are added to 999,500-par-t-portions of Bases 13-16 to yield fungicidal compositions which contain SOD-parts per million of the o-toluidine chromium tricarbonyl.

Exarnple VII Methylbenzoate chromium tricarbonyl, 100 parts, is added to 999,900 parts of Base 2 to yield a fungicidal composition which contains 100 parts per million of methylbenzoate chromium tricarbonyl.

Similar compositions are prepared by adding 100-partportions to 999,900-part-portions of Bases 216.

Other bases which are comparable to those defined and illustrated above which may be employed in this invention are White Ointment U.S.P and Yellow Ointment U.S.P.

The fungicidal compositions definedand illustrated above do not require a surface active agent. However, minor amounts (from about 1 to about 5 parts by weight per each 100 parts of oleaginous substance) of surface active agents can be employed if desired.

Solid, semi-solid, or thick, liquid emulsions comprise a second preferred type of fungicidal composition provided by this invention. The emulsions may be either an oil-in-Water or water in-oil type. Besides a fungitoxic amount of at least one arene chromium tricarbonyl, these compositions contain an oleagirrous substance of the type described above'and, for each 100 parts thereof, from about to about 7500 parts of water. Preferably, these compositions contain from about to 300 parts of water and most preferably, from about to about parts. Usually, distilled Water is employed in these formulations. However, scented Water such as rose water and the like can be employed if desired.

If desired, these compositions may contain other ingredients besides the oleaginous substance, water, and fungicidal agents. A preferred type of composition is an alcohol-water-oil emulsion which contains a higher alcohol of the type described above. Preferred alcohols are cetyl and stearyl alcohol. Usually from about 1 to about 1500 parts of alcohol of this type is employed for each 100 parts of oleaginous material. Preferred compositions contain from about 5 to about 100 parts of alcohol, and most preferably, from about 8 to about 30 parts.

If desired, the alcohol-water-oil emulsions may contain a surface active agent. The exact nature of the surface active agent is not critical, provided that it is compatible with the other ingredients in the composition.

Anionic surface active agents such as the alkali metal salts of long-chain organic sulfates, sulfonates, and the like are preferred. Highly preferred surface active agents are illustrated by sodium chlorocetane sulfate, sodium- N-oleyl N-methyl taurine, sodium cetyl sulfonate, sodium lauryl sulfate, and the like.

A surface active quantity of the surfactant is employed. Usually from about 2 to about 200 parts of surface active agent is used per each 100 parts of oleaginous substance. Preferably, from 2 to about 8 parts are employed.

If desired, below may contain minor amounts of an ester. Preferably, the esters are derived from acids having from about 12 to about 20 carbon atoms and from alcohols having from about 3 to about 10 carbon atoms. Highly the alcohol-water-oil bases illustrated I 7 preferred esters of this type are illustrated by butyl stearate, diglycol distearate, trihyd'roxyethylamine stearate, diglycol dilaurate, diglyeol dioleate, propyleneglycol-300 monostearate, and the like. The latter com- 8 wherein R and R are alike or difierent and selected from the class consisting of hydrogen and alkyl groups having one to about four carbon atoms; [9 is an integer having the value to one; R is selected from the class consisting of pound is a stearic acid ester of a propyleneglycol polyhydrogen and alkyl groups having one to about 4 carbon mer having a molecular Weight of about 300. Usually atoms, and c is an integer having the value 0 to 3, such from about 5 to about 15 parts of an ester per each 100 that when c=3, a=0 and 17:0, and parts of oleaginous substance is employed. Preferably (2) As a carrier therefor, an emulsion base comprising from 6 to 13 parts are used, and most preferably from an oleaginous substance and, per each 100 parts of said about 8 to about 11 parts. oleaginous substance, from about 1 to about 30 parts of Minor amounts of other ingredients can be employed in a higher alcohol having from about 13 to about 30 carthe alcohol-oil-Water emulsion bases illustrated below. bon atoms; from about 95 to about 310 parts of water, A preferred ingredient is a polyhydric alcohol having from and from about 2 to about 6 parts of an anionic surface about 2 to about 4 carbon atoms. Preferred alcohols of active agent. this type are propyleneglycol and glycerol. Preservatives 15 Highly preferred compounds of this type are further such as benzoate of soda, metal-p-hydroxy 'benzoate, characterized in that they contain from about 10 to propyl-p-hydroxy benzoate, and the like can be employed about 50 parts of an inert opaque solid. Other highly if desired. preferred compositions are further characterized in that As with the anhydrous compositions described above, they contain from about 0.001 to about 2% of a hindered the alcohol-water-oleaginous substance emulsions em- P ployed in this invention preferably contain aninert, opaque B11865 Containing a long-Chain 1111601101, Water, and all solid and/ or a hindered phenol. Phenols and inert opaque Oleaginous Substance from which the fungicidal p olid of th type d ib d above are l d i thi tions of this embodiment are derived, are illustrated beembodiment. In general, the same concentration of these substances is used although greater or lesser amounts can BASE 17 be employed if desired. Thus, a preferred embodiment of this invention comprises a fungitoxic composition com- C l h l 1500 t d 100. parts f b s are P melted together. Thereafter, 1000 parts of propylenegly- AS a Prlnclpal act-1V8 lllgl'edleflt, fungllloxlc col is added and the resultant mixture heated to about amount of an arene Group VIB metal tricarbonyl having 5 C I another veSseL 200 Parts of Sodium laurylsulthe formula fate are dissolved in 7200 parts of Water heated to C. Yb R0 The oil phase (at 65 C.) is then added to the water phase slowly and with constant gentle stirring. Stirring Mwoh is continued until an ointment-like consistency results.

35 Other alcohol-Water oleaginous substance bases are X/ illustrated in Table 2 wherein the numbers in the columns (I) are by weight.

TABLE 2 Base Ingredient Petrolatum (white) 75.5 100 100 100 100 100 74.2 82.6 100 Cocoa butt 24. 5 25. 8 Lanolin (anhydrous) Mineral O Carbowax 4000.--- Beesw Vegetable O Methyl py oxybenzoate py D-hydroxynen nah: B orax- Propylene glyenl Glycerol Perfume Triethanolamine (trihydroxyethylamine) Rose Water- Water 1 As desired.

BASE 32 A base is prepared by adding 50 parts of bentonite to 100 parts of Base 22 and thoroughly mixing.

BASE 33 A base is prepared by adding 25 parts of fullers earth to parts of Base 23 and thoroughly mixing.

9 BASE 34 To 1000 parts of Base 21 is added and thoroughly blended parts of 4,4'-methylenebis(2,6-ditert-butylphenol). A similar base is prepared by adding identical parts of the phenol and Base 31 and thoroughly mixing.

BASE 35 One thousand parts of Base 18 is added and thoroughly blended with 2 parts of 4,4-methylenebis(2,6-diisopropylphenol).

Example VIII Methylbenzoate chromium tricarbonyl, 100 parts, is added to 999,900 parts of Base 18 and thoroughly mixed therewith. The resultant fungicidal composition contains 100 parts per million of methylbenzoate chromium tricarbonyl. In a similar manner, fungicidal compositions containing 50, 100, 300, 500'and 700 parts per million of methylbenzoate chromium tricarbonyl are prepared by thoroughly blending the requisite amount of the carbonyl with Base 18.

Similarly, fungicidal compositions containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20, and 30 percent of methylbenzoate chromium tricarbonyl are prepared by adding the requisite portions of the carbonyl to the required portion of Base 18.

Example IX o-Xylene chromium tricarbonyl, 100 parts, is added to 999,900parts of Base 19 and thoroughly mixed therewith. The resultant fungicidal composition contains 100 parts per million of o-xylene chromium tricarbonyl. In a similar manner, fungicidal compositions containing 50, 100, 300, 500, and 700 parts per million of o-xylene chromium tricarbonyl are prepared by thoroughly blending the requisite amount of the carbonyl with Base 19.

Similarly, fungicidal compositions containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20, and 30 percent of o-xylene chromium tricarbonyl are prepared by adding the requisite portions of the carbonyl to the required portion of Base 19.

Example X p-Xylene chromium tricarbonyl, 100 parts, is added to 999,900 parts of Base 20 and thoroughly mixed there-with. The resultant fungicidal composition contains 100 parts per million of p-xylene chromium tricarbonyl. In a similar maner, fungicidal compositions containing 50, 100, 300, 500, and 700 parts per million of p-xylene chromium tricarbonyl are prepared by thoroughly blending the requisite amount of the carbonyl with Base 20.

Similarly, fungicidal compositions containing 0.1-, 0.5, 1, 3, 5,7, 10, 15, 20, and 30 percent of p-xylene chromium tricarbonyl are prepared by adding the requisite portions of the carbonyl to the required portion of Base 20.

Example XI o-Toluidine chromium tricarbonyl, 100 parts, is added to 999,900 parts of Base 21 and thoroughly mixed therewith. The resultant fungicidal composition contains 100 parts per million of o-toluidine chromium tricarbonyl. In a similar manner, fungicidal compositions containing 50, 100, 300, 500, and 700 parts per million of o-toluidine Example XII Fungicidal compositions containing 500 parts per million of chlorobenzene chromium tricarbonyl are prepared by adding SOO-part-portions of the carbonyl to 999,500 part-portions of Bases 22-35.

Similar compositions containing 500 parts per million to 999,700-part portions of Bases 22-35.

of arene chromium tricarbonyl are prepared by adding 500 part-portions of aniline chromium tricarbonyl, dimethylaniline chromium tricarbonyl, anisole chromium tricarbonyl, mesitylene chromium tricarbonyl, methylbenzoate chromium tricarbonyl, benzene chromium tricarbonyl, acetophenone chromium tricarbonyl, and benzophenone chromium tricarbonyl, to 999,500-part portions of Bases 22-35.

Similar fungicidal compositions are prepared by adding 300-part portions of toluene chromium tricarbonyl These compositions contain 300 parts per million of the, fungicidal arene chromium tricarbonyl. Similarly, methylbenzoate chromium tricarbonyl, 50-part portions, is added to 999,- 950=part portions of Bases 22-35 to prepare fungicidal compositions which contain 50 parts per million of methylbenzoate chromium tricarbonyl.

Another preferred type of fungicidal composition comprising an emulsion contains a fungitoxic amount of an arene Group VIB metal tricarbonyl in an emulsion which contains an oleaginous substance, an ester, and water. The emulsion bases of this embodiment are similar to those above except they do not contain a long-chain alcohol. In general, bases of this type contain, per each parts of oleaginous substance, from about 10 to about 1500 parts of an ester derived from a carboxylic acid having from about 12 to about 20 carbon atoms, and an alcohol having from about 3 to about 6 carbon atoms. Preferably, from about 11 to about 400 parts of ester are employed, and most preferably, from about 11 to about 35 parts of ester.

As with the esters employed in the alcohol-oil-water emulsions described and illustrated above, there is no exact limitation on the number of carbon atoms in the alcohol or acid portion of the ester. All that is required is that the ester yield a suitable emulsion when combined with the oleaginous substance and water. Highly preferred esters are illustrated by diethyleneglycol monostearate, diglycol stearate, glyceryl monostearate, isopropylmyristate, sorbitane monooleate, polyethyleneglycol 1000 monostearate, and the like. Polyethyleneglycol 1000 is an alcohol having the molecular weight of 1000, derived by polymerizing ethyleneglycol. The specific esters mentioned immediately above can be employed in the preparation of bases such as those illustrated by Bases 17-35, and similarly, the esters incorporated in those bases can be employed in the preparation of oleaginous substance-ester-water emulsions of the type illustrated below.

The ester-water-oil emulsions illustrated below, like the anhydrous and alcohol-water-oil preparations described and illustrated above, preferably contain an opaque inert insoluble substance and/ or a hindered phenol of the types described and illustrated above. In general, the amounts of the phenol and opaque substance are identical to the amounts employed in the above compositions. However,

higher and lower quantities can be employed if desired. Thus, a preferred embodiment of this invention com prises a fungicidal composition containing wherein M is a metal of Group VIB of the Periodic Table; X is a halogen; a is an integer having the value 0 to 1; Y is selected from the class comprising NRiR OR1, OR1, CN, CH OH wherein R and R are alike or difierent and selected from the class consisting of hydrogen and alkyl groups having one to about 4 carbon atoms; b is an integer having the value to 1; R is selected from the class consisting of hydrogen and alkyl groups having one to about 4 carbon atoms, and c is an integer having the value 0 to 3, such that when 0:3, (1:0 and 12:0, and

(2) As a carrier therefor, an emulsion base comprising an oleaginous substance and, for each 100 parts per weight of said oleaginous substance, from about to about 1500 parts of an ester derived from a carboxylic acid having from about 13 to about carbon atoms and an alcohol having from about 3 to about 6 carbon atoms; and from about 11 to about 7500 parts of water.

Highly preferred compositions of this embodiment are further characterized in that they contain from about 10 to about 50 parts of an insoluble inert opaque solid.

Other highly preferred compositions of this embodiment are further characterized in that they contain from about 0.001 to about 5% of a hindered phenol having Formula II.

Bases employed in this embodiment are illustrated by the bases of Table 3. In the table, the figures in the columns are parts by Weight.

TABLE 3 Ingredient Petrolatum- Suliated hydrogenated castor oil Sperrnaceti an in. Liquid petrolatum- Paratfin wax- Mineral .oil Diethyleneglycol monostearate Diglycol stearat-e Glycerol monostearate Polyethyleneglycol 1000-m0nostearate Isopropyl myri mm Sorbitan monooleate- Stearie acid. Preservative Propylene glycoL Glycerin--- Water Example XIII Example XIV o-Xylene chromium tricarbonyl, 30 parts, is added to 999,970 parts of Base 38 to yield a fungicidal composition having 3 0 parts per million of arene chromium tricarbonyl.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500 and 700 parts per million of o-xylene chromium .tricarbonyl are prepared. More concentrated foams containing 0.1, 0.5, 1, 3, S, 7, 10, 15, 20, and 30 percent of arene chromium tricarbonyl are prepared by adding the requisite quantity of o-xylene chromium tricarbonyl to Base 38.

12 Example XV p-Xylene chromium tricarbonyl, 30 parts, is added to 999,970 parts of Base 37 to yield a fungicidal composition having 30 parts per million of arene chromium tricarbonyl.

In a similar manner, usiug'the same base, funigicidal of p-xylene chromium tricarbonyl toBase 37.

Example XVI o-Toluidine chromium tricarbonyl, 30 parts, is added to 999,970 parts of Base 36 to yield a fungicidal composition having 30 parts per million of arene chromium tricarbonyl.

In a similar manner, using the same base, fungicidal compositions containing 5 0, 100, 300, 500 and 7 00 parts per million of o-toluidine chromium tricar-bonyl are prepared. More concentrated foams containing 0.1, 0.5, :l, 3, 5, 7, 10, 15, -20, and 30 percent of arene chromium tricanbonyl are prepared by adding the requisite quantity of o-toluidine chromium tricarbonyl to Base 36.

Example XVII Pungicidal compositions are prepared by adding 100- part-portions of me'thylbenzoate chromium tricanbonyl to 9900-part-portions of Bases 36, 37, 39 and 40. The compositions contain 1% of methylbenzoate chromium tricanbonyl. Similar fungicidal compositions containing 0.5% of an arene chromium tricanbonyl are prepared by adding 50-part portions of aniline chromium tricarbonyl, toluene chromium tricarbonyl, chlorobenzene chromium tricarbonyl, benzene chromium tricarbonyl, and mesitylene chromium tricarbonyl, to 99'50-part portions of Bases 36-40.

Similar compositions are prepared by adding 20-part portions of bentonite to -part portions of Bases 3 6-40 and thoroughly mixing. Thereafter, 99.5-part portions of the bentonite-containing bases are then thoroughly blended with (LS-part portions of methylbenzoate chrornium tricarbonyl, o-Xylene chromium tricarbonyl, p-Xylene chromium tricarbonyl, and o-toluidine chromium tricarbony-l.

Example XV'IH 4,4'-methylenebis(2,6-di-tert-butylphenol), 025 part, 20 parts of fullers earth, and 79.75 parts of Base 38 are thoroughly blended. The resultant base is then divided into five 9.5-part portions. To the first 9.5-par-t portion is added 0.5 part of methylbenzoate chromium tricarbonyl. To each of the other 9.5-part portions is added 0.5 part of o-toluidine, p-xylene, o-Xylene, and aniline chromium tricarbonyl respectively. The resultant fungicidal compositions contain 5% of the respective fungitoXic arene Group VIB metal tricarbonyl.

Other bases which do not have an oleaginous substance can be employed to prepare preferred fungicidal compositions of this invention. Thus, another preferred embodiment of this invention comprises:

(1) As a principal active ingredient, a fungitoxic amount of at least one arene Group VIB metal tricarbonyl having the formula wherein M is a metal of Group VIB of the Periodic Table,

wherein R and R are alike or different and selected from the class consisting of hydrogen and alkyl groups having one to about 4 carbon atoms; 1) is an integer having the value to 1; R is selected from the class consisting of hydrogen and alkyl groups having one to about 4 carbon atoms, and c is an integer having the value 0 to 3, such that when 0:3, (1:0 and b=0, and

(2) As a carrier therefor, an ester-water emulsion comprising an ester derived from an acid having from about 13 to about 20 carbon atoms and an alcohol having from about 3 to about -6 carbon atoms and, per each 100 parts of ester, from about 20 to about 100 parts ofan insoluble, inert, opaque solid, and from about 300 to about 780 parts of water.

Highly preferred compositions of this type are further characterized in that they contain from about 0.001 to about of a hindered phenol. The esters and insoluble inert opaque solids described above can be employed in this embodiment. Bases employed in this embodiment are illustrated by those in Table 4 wherein the figures in the columns are parts by weight.

Methylbenzoate chromium tricarbonyl, 30 parts, is thoroughly mixed with 999,970 parts of Base 41. The resultant fungicidal composition has a concentration of arene chromium tricarbonyl equal to 30 parts per million.

In a similar manner, using the same base, fungicidal com-positions containing 50, 100, 300, 500, and 700 parts per million of methylbenzoate chromium tricarbonyl are prepared.

More concentrated foams containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20 and 30 percent of arene chromium tr-icarbonyl are prepared by adding the requisite quantity of methylbenzoate chromium tricarbonyl to Base 41.

Example XX o-Toluidine chromium tricarbonyl, 30 parts, is thoroughly mixed with 999,970 parts of Base 43. The resultant fungicidal composition has a concentration of arene chromium tricarb-onyl equal to 30 parts per million.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500, and 700 :parts per million of o-toluidine chromium tricarbonyl are prepared.

More concentrated foams containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20, and 30 percent of arene chromium tricar-bonyl are prepared by add-ing the requisite quantity of o-toluidine chromium tricarbonyl to Base 43.

Example XXI o-Xylene chromium tricarbonyl, 30 parts, is thoroughly mixed with 999,970 parts of Base 44. The resultant fungicidal composition has a concentration of arene chromium tricarbonyl equal to 30 parts per mill-ion.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500, and 700 parts per million of o-xylene chromium t-ricarbonyl are prepared.

More concentrated foams containing 0.1, 0.5, 1, 3, 5, 7, 10, 15, 20, and 30 percent of arene chromium tricarbonyl are prepared by adding the requisite quantity of o-xylene chromium tricarbonyl to Base 44.

Example XXII p-Xylene chromium tricarbonyl, 30 parts, is thoroughly mixed with 999,970 parts of Base 44. The resultant fungicidal composition has a concentration of arene chromium tricarbonyl equal to 30 parts per million.

In a similar manner, using the same base, fungicidal compositions containing 50, 100, 300, 500, and 700 parts per million of p-xylene chromium tricarbonyl are prepared.

More concentrated foams containing 0.1, 0.5, '1, 3, 5, 7, 10, 15, 20, and 30 percent of arene chromium tricarb'onyl are prepared by adding the requisite quantity of p-xylene chromium tricarbonyl to Base 44.

Example XXIII Base 42 is prepared with 700 parts of water. To'a 980-part portion of the resultant base is added 20 parts of 4,4'methylenebis(2,6-di-tert-butylphenol). The resultant stabilized base is then divided into eight 97-part portions. To each port-ion is added 3 parts of methylbenzoate chromium tricarbonyl, o-toluidine chromium tricarbonyl, o-xylene chromium tricarbonyl, p-xylene chromium tricar-bonyl, aniline chromium tricarbonyl, benzene chromium tricar-bonyl, chlorobenzene chromium tricarbonyl, and toluene chromium tricarbonyl respectively. The resultant fungicidal composition contains 3% by weight of an arene chromium tnicarbonyl.

To a further 97-part portion of the stabilized base is added 1.5 parts of o-toluidine chromium tricarbonyl and 1.5 parts of methylbenzoate chromium tricarbonyl. The resultant fungicidal composition contains 3% by weight of a mixture of arene Group VIB metal tricarbonyls.

As reported in my copending application Serial No. 161,367, the arene Group VIB metal tr-icarbonyls are especially efficacious in treating fungi which are pathogenic to animals and man. This has been demonstrated by the following serial dilution tests.

SERIAL DILUTION TESTS Arene chromium tricarbonyls were evaluated for fungicidal activity by the serial dilution test of Burlingameand Reddish, J. Lab. Clin. Med, 24, page 765, 1939. The test fungi used in this case were T richophyton interdigitale, T richophyton rubrum, T richophyton schoenleinii, Microsporum audouini, Epidermop hyton floccosum, Microsporum gypseum. These fungi were grown in Difcos Sabourauds liquid medium, pH 4.7. Sample preparation SERIAL DILUTION {Fungi pathogenic to man and animals.

Minimum efiective concentration in parts/million] Ma Mg Tr Ef Ts Ti CBHSNHZ :(00); 12s 64 32 CfiHfi-CHa Cr(00 512 128 2 0CH3C5H4CH3C CO)3 32 32 32 CICEH5CT(OO)3OI(CO)3 128 256 16 0CH;CaHr-NH2 CI'(CO)3 16 32 8 ]3CH3C5H4-CH3 (moon..- 64 128 s mCH3CuI'I4-OH3 Cl (C 0);; 16 512 l6 CH3O-(%C5H5 (moon 64 4 1 2 4 Calls Cr(CO) 512 512 4 64 12s 1,3,5(OH3)3C6H3C1'(CO)3 512 512 64 12s 512 *Ma=Mt'crosporum audouzm'.

Mg=Micrasp0rum gypseum.

Tr= Trichophyttm rubrum.

Ts= Trychophyton schoenleinii.

Ti: Trichophyton interdigitale.

In a similar manner, the compositions of this invention 4. The composition of claim 2 wherein said inert solid are active against fungi. is bentonite.

The fungicidal compositions provided herein are prefer- 5. A composition of claim 2 having from about 0.001 ably excluded from excessive light and exposure to air. to about 2 percent by Weight of a phenol having the Preferably they are stored in opaque, closed containers. formula The fungicidal compositions of this invention are em- R1 R1 ployed by applying them to the locus of the fungi. In I H I some instances, especially when the fungicidal infection is somewhat severe, more than one application may be I required. In some cases, it is desirable to cover the H infected part with a sterile dressing after applying the composition.

The compositions are especially effioacious against wharam me l designated by R1 R2 are alkyl I fun wh'ch r i th eni to animals and man such as groups contammg from 3 8 Carbon atoms are 1 6 further charactenzed by being branched on their alpha Mzcrosporum audoumz, Mzcrosporum gypseum, T rzchm rb v phyto rubmm Epidermophymn Floccosum Trick fi t z iiiiiosition of claim 5 wherein said phenol is {51(20): schoenlemu, T rzchophyton mterdzgztale, and the y y p f Having fully described the novel compositions of this A fim'glcldzil P f P Fq i invention, the method of employing them, and their many 40 pfrmclpa acmge i m g i i utilities, I desire that the scope of this invention be limited g an arene C mmmm mcar Onyl avmg only by the lawful scope of the appended claims. t 6' 0mm a I claim: b R,

1. A fungicidal composition comprising (1) as a principal active ingredient, a fungitoxic o amount of a compound having the formula M0 wherein X is a halogen; a is an integer having the p a value 0 to 1; Y is selected from the class comprising 8 wherein X is a halogen; a is an integer having the value 0 to 1; Y is selected from the class comprising NRlRz CR1 and G 1 wherein R and R are independently selected from ll l the class consisting of hydrogen and alkyl groups and G OR having one to 4 carbon atoms; b is an integer havwherein R and R are independently selected from ing the value 0 to 1; R is selected from the class the class consisting of hydrogen and alkyl groups consisting of hydrogen and alkyl groups having one having one to 4 carbon atoms; 17 is an integer having to 4 carbon atoms, and c is an integer having the the value 0 to 1; R is selected from the class convalue 0 to 3, such that when 0:3, a=0 and b=0; sisting of hydrogen and alkyl groups having one to 4 and carbon atoms, and c is an integer having the value (2) as a carrier therefor, an emulsion comprising a 0 to 3, such that when c=3, a=0 and 15:0; and non-toxic, non-drying, inert oleaginous substance (2) as a carrier therefor, a non-toxic, nondrying, and, for each 100 parts of said oleaginous sub-,

inert oleaginous substance, and, for each 100 parts stance, by weight of said oleaginous substance, from about from about one to about 31 parts of a monohydric 5 to about 30 parts of an alcohol having from about alcohol having from about 13 to about 30 car- 16 to about 30 carbon atoms. bon atoms,

2. A composition of claim 1 being furthercharacterfrom about 2 to about 6 parts of an alkali metalized in that said carrier com-prises, per each 100 parts containing anionic surfactant, and of said oleaginous substance, from about 10 to about 50 from about to about 310 par-ts of water. parts of an inert, opaque, insoluble non-toxic solid. 8. A composition of claim 7 being further character- 3. A composition of claim ,2 wherein said inert solid ized in that said carrier contains, for each parts of is stearic acid. 75 said oleaginous substance,

17 from about 8 to about 12 parts of an ester derived from an acid having from about 12 to about 20 carbon atoms and an alcohol having from about 3 to about 6 carbon atoms.

9. A composition of claim 8 being further characterized in that said carrier also contains from about 10 to about 50 parts of an inert, insoluble, opaque, non-toxic solid.

10. A composition of claim 9 being further characterized in that it contains from about 0.001 to about 2 percent of a phenol having the formula wherein the groups designated by R and R are alkyl groups containing from 3 to 8 carbon atoms and are further characterized by being branched on their alpha carbon atoms.

11. A fungitoxic composition comprising (1) as a principal active ingredient a fungicidal amount of an arene chromium tricarbonyl having the formula:

wherein X is a halogen; a is an integer having the value to 1; Y is selected from the class comprising wherein R and R are independently selected from the class consisting of hydrogen and alkyl groups having one to 4 canbon atoms; b is 'an integer having the value 0 to 1; R is selected from the class consisting of hydrogen and alkyl groups having one to 4 carbon atoms, and c is an integer having the value 0 to 3, such that when c=3, a=0 and b=0; and

(2) as a carrier therefor, a substantially long chainalcohol-free emulsion comprising a non-toxic, nondrying inert, oleaginous substance, and per each 100 parts of said oleaginous substance,

from about 10 to about 1500 parts of an ester derived from a long-chain carboxylic acid having from about 13 to about 20 carbon atoms and an alcohol having from about 3 to about 23 carbon atoms, and

from about 80 to about 7500 parts of water.

12. A composition of claim 11 being further characterized in that said carrier comprises, per each 100 parts of said oleaginous substance, from about 10 to about 50 parts of an insoluble inert, opaque, solid.

13. A composition of claim 12 containing from about 0.001 percent to about 2 percent of a phenol having the formula I H I R: R2

wherein the groups designated by R and R are alkyl groups containing from 3 to 8 carbon atoms and are further characterized by being branched on' their alpha carbon atoms.

14. A fungicidal composition comprising (1) as a principal active ingredient, a fungitoxic amount of an arene chromium tricarbonyl having the formula wherein X is a halogen; or is an integer having the value 0 to 1; Y is selected from the class comprising O O NR Rz, -OR1, %R1 and (LJOR| wherein R and R are independently selected from the class consisting of hydrogen and alkyl groups having one to 4 carbon atoms; b is an integer having the value 0 to 1; R is selected fromlthe class consisting of hydrogen and alkyl groups having one to 4 carbon atoms, and c is an integer having the value 0 to 3, such that when c=3, a=0 and b=0; and (2) as a carrier therefor, an emulsion comprising an ester derived from a'car-boxylic acid having from about 13 to about 20 carbon atoms, and an alcohol having from about 3 to about 6 carbon atoms and, per each parts of said ester,

from about 20 to about 100 parts of an inert opaque insoluble solid and from about 330 to about 770 parts of water. 15. A composition of claim 14 comprising from about 0.001 to about 2 percent of a phenol having the formula H H, ago...

it I R2 R2 wherein the groups designated by R and R are alkyl groups containing from 3 to 8 carbon atoms and are further characterized by being branched on their alpha carbon atoms.

16. A methodfor treating fungi comprising treating the locus of the fungi with the composition of claim 1. 17. A method of combating fungi comprising treating the locus of the fungi with the composition of claim 7. 18. A method of combating fungi comprising treating the locus of the fungi with the composition of claim 11. 19. A method of combating fungi comprising treating the locus of the fungi With the composition of-claim 14.

No references cited.

LEWIS GO'ITS, Primary Examiner.

S. K. ROSE, Assistant Examiner. 

1. A FUNGICIDAL COMPOSITION COMPRISING (1) AS A PRINCIPAL ACTIVE INGREDIENT, A FUNGITOXIC AMOUNT OF A COMPOUND HAVING THE FORMULA 